Platelet-derived growth factor-AA and -alpha receptor expression suggests an autocrine and/or paracrine loop in osteosarcoma

Platelet-derived growth factor (PDGF) is a major mitogen and chemotactic fa ctor for mesenchymal cells such as fibroblasts, smooth muscle cells, and os teoblasts. PDGF exists as disulfide-linked homo- or heterodimers composed o f two polypeptide chains encoded by distinct genes, designated PDGF-A and P DGF-B. Upon binding to its tyrosine kinase receptor PDGF-alpha, especially PDGF-AA stimulates the proliferation of osteoblastic cells and may exert au tocrine and paracrine effects in regulating bone-forming processes. The pur pose of this immunohistochemical study was to determine the expression of P DGF-AA and PDGF-alpha receptor in benign and malignant neoplastic bone lesi ons. Polyclonal antibodies to PDGF-AA and PDGF-alpha receptor were used on paraffin sections of 23 osteosarcomas and 17 osteoblastomas. Immunostaining was assessed quantitatively by evaluating the percentage of reactive tumor cells. In osteosarcomas, the mean expression of PDGF-AA and PDGF-alpha rec eptor was 33.97% (range, 2 to 80%; SD, 24.26%) and 27.13% (range, 3.2 to 72 %; SD, 18.38%), respectively. Osteoblastomas showed significantly lower exp ression of PDGF-AA than osteosarcomas (mean, 15.71%; range, 5 to 34%; SD, 9 .43%; P = .019). Although the mean expression of PDGF-alpha receptor in ost eoblastomas was much lower than in osteosarcomas (mean, 17.55%; range, 3.6 to 26.8%; SD, 6.47%), the difference was not significant (P = .122). For os teosarcomas, Spearman correlation coefficient (two-tailed) revealed a signi ficant correlation between the expression of PDGF-AA and PDGF-alpha recepto r (r = .688), which was not the case for osteoblastomas (r = .267). These d ata suggest that in contrast to osteoblastoma, the growth of osteosarcoma m ay be supported by the coordinate expression of the potent mitogenic growth factor and its receptor that exert their functions by autocrine and paracr ine mechanisms.